Biology subjects

Lazar, V.

Publications and source records attributed to Lazar, V..

3 recordsLinked to original sources

bioRxiv2024

Unveiling Humoral and Cellular Immune Responses to SARS-CoV-2 in Head and Neck Cancer: A Comparative Study of Vaccination and Natural Infection in Romania

BackgroundTo fill the knowledge gap regarding the antiviral immunity in oncologic patients, we performed a comparative study on natural/vaccine-induced SARS-CoV-2 immunity in head and neck cancer (HNC) in Romania. MethodsBlood was collected from HNC (n=49) and controls (n=14), stratified as vaccinated (RNA/adenovirus-based vaccines), convalescent, and hybrid immunity. Plasma IgG/IgA antibodies (Abs) against Spike (S1/S2), receptor binding domain (RBD), and nucleocapsid (NC), and cytokines were quantified using the MILLIPLEX(R) technology. The frequency/phenotype/isotype of RBD-specific B-cells were studied by flow cytometry using tetramers (Tet++). Cell proliferation in response to Spike/NC peptides was monitored by carboxyfluorescein succinimidyl ester (CFSE) assay. A longitudinal follow-up was performed on n=25 HNC. FindingsLevels of S1/S2/RBD-specific IgG/IgA Abs were similarly high in HNC and controls, but significantly increased in convalescent/hybrid versus vaccinated HNC. NC-specific IgG/IgA Abs were only detected in convalescent/hybrid immunity groups. The frequency of Tet++ B-cells in HNC was similar to controls, irrespective of the immunization status, and correlated positively with RBD IgG/IgA Abs and negatively with the time since immunization (TSI). Compared to total B-cells, Tet++ were enriched in CD27+ memory phenotype and IgG/IgA isotype. A linear regression model identified Spike S2 IgG and NC IgA Abs as strong positive predictors of Tet++ frequencies, while IL-6 was a marginally significant negative predictor. Tet++ frequency remained stable at median TSI of 341 versus 117 days, despite a decline in memory phenotype. InterpretationHNC participants mount efficient and durable SARS-CoV-2 humoral immunity, with RBD-specific IgG/IgA Abs and Tet++ B-cells representing the major immunization outcomes.

immunology↗

bioRxiv2020

Whole exome precision oncology targeting synthetic lethal vulnerabilities across the tumor transcriptome

Precision oncology has made significant advances in the last few years, mainly by targeting actionable mutations in cancer driver genes. However, the proportion of patients whose tumors can be targeted therapeutically remains limited. Recent studies have begun to explore the benefit of analyzing tumor transcriptomics data to guide patient treatment, raising the need for new approaches for systematically accomplishing that. Here we show that computationally derived genetic interactions can successfully predict patient response. Assembling a broad repertoire of 32 datasets spanning more than 1,500 patients and including both tumor transcriptomics and response data, we predicted the response in 17 out of 21 targeted and 8 out of 11 checkpoint therapy datasets across 8 different cancer types with considerable accuracy, without ever training on these datasets. Analyzing the recently published multi-arm WINTHER trial, we show that the fraction of patients benefitting from transcriptomic-based treatments could potentially be markedly increased from 15% to about 85% by targeting synthetic lethal vulnerabilities in their tumors. In summary, this is the first computational approach to obtain considerable predictive performance across many different targeted and immunotherapy datasets, providing a promising new way for guiding cancer treatment based on the tumor transcriptomics of cancer patients.

cancer biology↗

bioRxiv2019

Chemical-genetic profiling reveals cross-resistance and collateral sensitivity between antimicrobial peptides

Antimicrobial peptides (AMPs) are key effectors of the innate immune system and promising therapeutic agents. Yet, knowledge on how to design AMPs with minimal cross-resistance to human host-defense peptides remains limited. Here, with a chemical-genetic approach, we systematically assessed the resistance determinants of Escherichia coli against 15 different AMPs. Although generalizations about AMP resistance are common in the literature, we found that AMPs with different physicochemical properties and cellular targets vary considerably in their resistance determinants. As a consequence, collateral sensitivity effects were common: numerous genes decreased susceptibility to one AMP while simultaneously sensitized to others. Finally, the chemical-genetic map predicted the cross-resistance spectrum of laboratory-evolved human-B-defensin-3 resistant lineages. Our work substantially broadens the scope of known resistance-modulating genes and explores the pleiotropic effects of AMP resistance. In the future, the chemicalgenetic map could inform efforts to minimize cross-resistance between therapeutic and human host AMPs.

microbiology↗